Implementing antibody-drug conjugates (ADCs) in HER2-positive breast cancer: State of the art and future directions Review
| Authors: | Ferraro, E.; Drago, J. Z.; Modi, S. |
| Review Title: | Implementing antibody-drug conjugates (ADCs) in HER2-positive breast cancer: State of the art and future directions |
| Abstract: | The development of anti-HER2 agents has been one of the most meaningful advancements in the management of metastatic breast cancer, significantly improving survival outcomes. Despite the efficacy of anti-HER2 monoclonal antibodies, concurrent chemotherapy is still needed to maximize response. Antibody-drug conjugates (ADCs) are a class of therapeutics that combines an antigen-specific antibody backbone with a potent cytotoxic payload, resulting in an improved therapeutic index. Two anti-HER2 ADCs have been approved by the FDA with different indications in HER2-positive breast cancer. Ado-trastuzumab emtansine (T-DM1) was the first-in-class HER2-targeting ADC, initially approved in 2013 for metastatic patients who previously received trastuzumab and a taxane, and the label was expanded in 2019 to include adjuvant treatment of high-risk patients with residual disease after neoadjuvant taxane and trastuzumab-based therapy. In 2020, trastuzumab deruxtecan (T-DXd) was the second approved ADC for patients who had received at least 2 lines of anti-HER2-based therapy in the metastatic setting. The success of these two agents has transformed the treatment of HER2-positive breast cancer and has re-energized the field of ADC development. Given their advanced pharmaceutical properties, next-generation HER2-targeted ADCs have the potential to be active beyond traditional HER2-positive breast cancer and may be effective in cells with low expression of HER2 or ERBB2 mutations, opening a spectrum of new possible clinical applications. Ongoing challenges include improving target-specificity, optimizing the toxicity profile, and identifying biomarkers for patient selection. The aim of this review is to summarize the principal molecular, clinical, and safety characteristics of approved and experimental anti-HER2 ADCs, contextualizing the current and future landscape of drug development. © 2021, The Author(s). |
| Keywords: | antibody-drug conjugate; her2-positive breast cancer; adcs; anti-her2 adcs; anti-her2 antibody conjugate; novel anti-her2 adcs |
| Journal Title: | Breast Cancer Research |
| Volume: | 23 |
| ISSN: | 1465-5411 |
| Publisher: | Biomed Central Ltd |
| Date Published: | 2021-08-11 |
| Start Page: | 84 |
| Language: | English |
| DOI: | 10.1186/s13058-021-01459-y |
| PROVIDER: | scopus |
| PMCID: | PMC8356386 |
| PUBMED: | 34380530 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 1 September 2021 -- Source: Scopus |
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